High dose Chemotherapy and peripheral blood stem cell transplant in
Lymphomas
1.0 Introduction
Although the majority of solid tumors when they are metastatic are incurable, many of them are chemosensitive, which helps in achieving good palliation with active treatment. Contrary to solid cancers, remissions obtainable in a wide variety of lymphomas, coupled with the dose response effect demonstrated in both laboratory and clinical studies, clearly suggests a possible role for high dose chemotherapy in a curative setting (1, 2). Sustained remissions, and possibly cure could be achieved using high dose chemotherapy (HDC) in certain subsets of patients (3-4). The main dose limiting factor of HDC myelosuppression, in fact myeloablation produced by usage of HDC. However, bone marrow transplant (BMT), and in recent years, peripheral blood stem cell transplant (PBSCT) has helped to circumvent this problem.
While the presence of primitive hematopoietic progenitor cells in peripheral blood has been recognized for a long time, its identification has been made easier with the facility to recognize and quantify CD 34+ positivity which is unique to the progenitor cells (5). However, the normal concentration of PBSC as shown by CD 34 + positive cells is only 0.1% of mononuclear cells, which is inadequate to reconstitute normal hematologic function after myeloablation (6). Apart from physiologic variations which are not of practical benefit in this context, it was recognized in 1970 that there is a 20 fold increase in circulating colony forming units of granulocyte / macrophages following chemotherapy (7). It then became possible to collect a sufficient yield of PBSC if the pheresis was timed appropriately after chemotherapy (8,9). Subsequent availability of the growth factors (G-CSF, GM-CSF) again demonstrated their capacity to increase the circulating population of PBSC by many folds (10-13). Combining the two approaches has a synergistic effect. PBSCT has not only been shown to be equivalent to BMT, but possibly even better, in terms of quicker recovery from myelosuppression (14). In addition, it is easier to perform, cheaper, potentially less hazardous, and may even reduce risk of contamination by tumor cells (14, 15).
HDC and Non Hodgkin's' Lymphoma (NHL) :
HDC has been used in NHL in a variety of settings: Up front and in first Complete Remission (CR) for cases both regarded as low, low intermediate risk or high intermediate and high risk (Appendix 12), in those who fail to achieve CR (patients with partial response (PR)v only after induction), or respond slowly to standard induction chemotherapy, and in relapse, whether or not there is demonstrated chemosensitivity (16-21). However, critical review of existing literature suggests that the only clear indication for HDC in NHL remains chemosensitive relapse, patients with primary refractory but chemotherapy sensitive to salvage therapy and possibly high risk cases in first CR although the results
of few available randomized trials have conflicting results (16-19). As transplant is usually limited to patients < 60 years, high risk is defined as having 2 risk factors as described in the Age Adjusted International Prognostic Index (22) (appendix 12). This applies to intermediate and high grade NHL as per the International Working Formulation (IWF) classification (23). WHO modification of REAL classification is now considered the most updated and current classification system in use in most of the institutions (24). The advantage of HDC in low grade NHL, specific high grade NHL subgroups like Burkitt's lymphoma, acute lymphoblastic lymphoma, and newer entities like mantle cell lymphoma remains to be proved. Those patients who relapse later, rather than sooner after first CR, are assumed to have biologically less aggressive, and potentially more chemosensitive disease. Moreover, relapsed NHL are rarely if ever, cured with conventional dose salvage chemotherapy. Therefore, HDC in NHL will be offered to patients with intermediate and high grade NHL (IWF) who relapse after an initial CR and demonstrate chemosensitivity to conventional salvage chemotherapy and those failed to achieve a CR after initial induction chemotherapy but proved to be sensitive to first line salvage chemotherapy
HDC and Hodgkin’s Disease (HD):
HD is curable with standard chemotherapy in upto 75% of cases (25). In those who relapse following CR, 20-30% may achieve long term cure with standard salvage regimes (26-27). It is known, however, that those who relapse within twelve months following CR, do poorly with salvage chemotherapy, than those who relapse after longer remission intervals (27-28). Patients relapsing within 12 months or those who are refractory to first-line chemotherapy are also unlikely to be cured with standard salvage regimes. However, if they demonstrate chemosensitivity to such regimes, HDC may offer them the best chance of cure (29-30). Therefore, those relapsing within 12 months of a CR or failed to achieve a CR after initial induction chemotherapy but proved to be sensitive to first line salvage chemotherapy will be offered HDC.
Timing of HDC / PBSCT in the management of both NHL and HD is an area of active research. HDC will be offered to patients with the diagnosis of Non-Hodgkin’s Lymphoma and Hodgkin’s lymphoma at times specified above and explained in details later. In the past most studies used International Working Formulation (IWF) (23) histologic subtype of intermediate and high grade NHL for transplant. Now WHO / REAL (24) classification will be used to classify lymphomas (Appendix 1).
2.0 Indications
2.1 Non-Hodgkin’s Lymphoma
Patients with following
pathology-Diffuse large cell lymphoma (includes diffuse mixed cell, diffuse large cell, immunoblastic)
T cell rich B cell lymphoma
Primary mediastinal large B-cell lymphoma Follicular center cell, follicular grade III
Anaplastic large cell lymphoma (systemic disease) Extranodal NK/T-cell lymphoma, nasal type Angioimmunoblastic T-cell lymphoma Hepatosplenic gamma/delta T-cell lymphoma Peripheral T-cell lymphoma
Enteropathy-type intestinal T-cell lymphoma Intravascular lymphomatosis
1. Patients with sensitive relapse, after achieving CR (for at least four weeks) to first line chemotherapy. (first priority)
2. Patients who achieved less than CR or had primary resistant / progressive disease but proved to be chemosensitive (partial response) on first line salvage chemotherapy, category commonly recognized as primary refractory / progressive but salvage sensitive disease. (second priority) 3. Patients relapsing after achieving CR (for at least four weeks) to first line chemotherapy not
sensitive to first line salvage chemotherapy but sensitive to second line salvage chemotherapy will be discussed on individual basis. (second priority)
2.2 Hodgkin’s Lymphoma
Patients with the following Hodgkin's lymphoma (Hodgkin's disease)
I. Nodular lymphocyte-predominant Hodgkin's lymphoma II. Classical Hodgkin's lymphoma
A. Nodular sclerosis Hodgkin's lymphoma
B. Lymphocyte-rich classical Hodgkin's lymphoma
C. Mixed cellularity Hodgkin's lymphoma
D. Lymphocyte depletion Hodgkin's lymphoma
1. Relapsed within 12 months after achieving complete remission, but proved to be chemosensitive (partial response) or have stable disease after first line salvage chemotherapy. (first priority)
2. Achieved only partial response or primary resistance to first line chemotherapy but proved to be chemosensitive to first line salvage chemotherapy (partial response) or have stable disease. (first priority)
3. Patients who have relapsed following two or more lines of chemotherapy induced complete remissions regardless of their disease free interval but proved to be chemosensitive (partial response) on salvage chemotherapy. (second priority)
4. Patients relapsing with in 12 months after achieving CR or relapsed after two or more lines of chemotherapy induced remissions (for at least four weeks), progressing on first line salvage chemotherapy but sensitive to second line salvage chemotherapy will be discussed on individual basis. (second priority)
2.3 Prioritization of Patients
Given the limited resources, ability to perform limited HDC / PBSCT at a given time, high cost but definitive benefit in a subset of patients, patients will be prioritize to undergo this procedure. For both HD and NHL, sensitive relapse after achieving a CR will be considered first priority and patients with primary refractory but salvage sensitive will be considered second priority.
3.0 Patient Selection
3.1 Inclusion Criteria
There are some features which are common to both NHL and HD for inclusion in HDC program. These are more related to tolerance to and feasibility of HDC per se, rather than the underlying disease. These will include:
1. Age 14 – 60 years (age > 60 and <70 will be considered on individual basis) 2. ECOG performance status ≤ 2
3. Adequate hematological function with absolute neutrophils > 1500, Platelets > 100,000 K 4. < 20% of bone marrow involvement at the time of harvesting / re-evaluation (see personal communication / emails to different institutions)
5. Normal renal, hepatic, and cardiac function (EF >50%) 6. Adequate pulmonary function (DLCO > 50% of predicted) 7. Informed Consent
8. HIV negative status
There are some features which are common to both NHL and HD for exclusion from HDC program:
1. > 20% bone marrow involvement at time of high dose chemotherapy 2. Central nervous system involvement
3. Pregnancy
4. Active, uncontrolled infections
5. Patients who are not mentally or psychologically fit for the procedure
4.0 Treatment Plan
The program will be in four stages:
1. Demonstrate chemosensitivity by salvage chemotherapy 2. Harvest stem cells from peripheral blood
3. Baseline work-up pre HDC
3. Administration of HDC and PBSCT and other supportive care
4.1 Demonstrating Chemosensitivity and Response Evaluation
Definition: Patients will be considered to have chemosensitive disease if they achieve partial or complete remission after two or more cycles of salvage chemotherapy. This will be done by giving 2-3 cycles of the standard salvage chemotherapy preferably ESAP (Etoposide, Solumedrol, Ara-c, Cisplatin) (31), regimen and assessing response thereafter:
Alternative regimes which may be used are IMVP-16 (Ifosfamide, Methotrexate, Etoposide) regime (32) or DHAP (Dexamethasone, Ara-C, Cisplatin) regime (33) (Appendix 2/3/4) or MIME (34). Assessment for response will be made after 2 -3 cycles. However, alternate regimes are not to be used routinely, and reasons for not using ESAP must be documented. It is encouraged to give 3 cycles of salvage chemotherapy before reassessment in patients with positive marrow involvement or bulky disease.
Full details of the above regimens are provided in Appendix 2
RESPONSE EVALUATION
Complete response = complete disappearance of all tumor for at least 4 weeks
Partial response = >50% to 99% reduction in the sum of the product, the diameters or measured lesions persisting for four weeks. No new lesions occurring.
No change / stable disease = reduction in the tumor size of <50% or an increase in the tumor size of less than 25%. No new lesions occurring.
Progressive disease = any increase of greater than 25% in the sum of the product of any measurable lesion or appearance of new lesions. Patient should have received at least 2 courses of therapy before designation of progression. An increase of 50% in the sum of the product or new lesions between 2 cycles will be considered progression.
4.2 PBSC Mobilization and Harvesting
All patients will have insertion of double lumen central venous subclavian catheter (Permacath Pheresis Catheter) . This will be retained until after HDC is completed. PBSC collection will be done through the central catheter, ideally following the 3rd or 4th cycle of the salvage chemotherapy regimen in patients who have demonstrated chemosensitivity. CBCD will be monitored daily after PBSCT, and G-CSF at doses of 5 mcg / kilogram body weight twice daily will be given subcutaneously, starting 24 hours after completion of chemotherapy (preferably rounded dose of 300 or 480 mcg vials) (35). When recovery from myelosuppression occurs, as shown by increase in total leukocyte count increasing to, and/or reaching a value of 1000 after nadir values, daily CD 34 + cell counts will be done. When this exceeds 20 CD34+cells/ul of the peripheral blood cell count, pheresis will be carried out for PBSC harvest. This may be repeated daily until a minimum of 2 x 106 CD 34+ cells / kilogram body weight (36), and preferably an average of 5 x 106 cells / kilogram body weight is collected (37). This will be frozen, and stored in liquid nitrogen. It is expected that average time for pheresis will be 7 - 10 days after chemotherapy. Each pheresis procedure is likely to last around 3 - 4 hours, and patients may require pheresis for 1-3 consecutive days.
4.3 Baseline Work-Up
These will be initiated upon identification of a potential candidate preferably during the period of chemosensitivity testing.
The work-up will focus on establishing the residual tumor burden, and ascertaining function of viscera to ensure safety of HDC and feasibility for pheresis. See Appendix 5 for details.
4.4 High Dose Chemotherapy Regimens
The BEAM regimen will be used (BCNU, Etoposide, Ara-C, Melphalan)(38-39) Alternative regimens: CBV ( Cyclophosphamide, BCNU, Etoposide) (4, 41-43)
Indications to use alternative regimen are either a contraindication to use any of the drugs of the BEAM regimen or if any of the drugs not available.
Patients will require special medical care and nursing during, and following HDC. These are summarized in the standing orders (Appendix 6 -11).
Full details of the BEAM and CBV regimens is provided in Appendix 6/7
4.5 PBSC Reinfusion
Following completion of HDC, PBSCT will be done by the bedside. The pheresis laboratory will be alerted about date of PBSCT at the time when HDC is commenced, and again 24 hours earlier. HDC should be timed so as to allow PBSCT on working days. While a nurse will be present during the whole procedure, the pheresis laboratory technician/s will be responsible for carrying out PBSCT. This includes checking of the patient's identity, premedication with Benadryl 50 mg and Hydrocortisone 100 mg (to be ordered by MD and given by nurse), thawing of stem cells at bedside, infusion of PBSC over 5-10 minutes (by nurse), monitoring for any immediate adverse reactions, and collecting samples for cell count, identification of contamination etc. Emergency medications including epinephrine, hydrocortisone, and diphenhydramine will be kept available by the bedside.
4.6 Post PBSC Infusion Care
Starting twenty four hours later, all patients will receive G-CSF 5 mg / kilogram body weight subcutaneously bid, (preferably rounded dose of 300 or 480 mcg vials) (35), continuing until ANC > 500 for at least 3 consecutive days or ANC >5000 x 1day . The average time for recovery from myelosuppression is expected to be 8-12 days following HDC. Neutropenic precautions as per defined hospital policy will be enforced when ANC levels fall below 500. Anti microbial regimes are as described in the standing orders or as per on going guidelines. Packed red blood cell and platelet transfusions will be given if hemoglobin and platelets fall below 80 and 10,000 respectively or as indicated clinically. Platelet transfusions may be given for higher values of platelets if there is active bleeding thought to be due to low platelets. All blood products will be irradiated pre transfusion. After recovery of blood counts (ANC > 500 and platelets > 20,000 without the use of transfusions for three consecutive days or ANC 5000 x 1day and platelets > 20,000), patients will be discharged. Patients can be discharged before full recovery of platelets if safe out patient housing and environment can be arranged. Follow-up will be done in the out-patient clinic at monthly intervals for the first three months if required for early post transplant related toxicity assessment otherwise every 3 month for 2 years, then every 6 months for 3 years and yearly there after at the discretion of attending physician, total of 5-10 years (Appendix 13). Treatment related early and long term toxicity, disease free survival, and overall survival will be calculated.
5.0 Role of the Bone Marrow Transplant Coordinator ( BMTC ) :
• When any patient is identified as a candidate for HDC, the BMTC will be informed by the treating physician.
• The BMTC will arrange the baseline work-up at the appropriate time in coordination with the treating team. Every effort will be made to perform most of the work up as an out patient.
• The BMTC will keep the pheresis laboratory informed regarding the timing of PBSC mobilizing program / pheresis, and the timing of HDC / reinfusion of PBSC, as agreed with attending physician/s. BMTC will also provide schedule of the above to the physicians.
• BMTC will coordinate in arranging appropriate timing of administration of salvage chemotherapy both as an inpatient and out patient
• The BMTC will help in monitoring of patients both pre and post HDC in the out-patient clinic. • The BMTC will arrange appropriate patient and family education
6. 0 Social Support
Every effort will be made to provide comprehensive social support by our social service team to better understand the social situation and needs of our patients to during this period of treatment. All patients will get proper social service evaluation for this purpose by an assigned member through BMTC.
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APPENDIX 1
Updated REAL/WHO Classification
B-cell
neoplasms-I. Precursor B-cell neoplasm: precursor B-acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL, LBL)
II. Peripheral B-cell neoplasms
a) B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma b) B-cell prolymphocytic leukemia
c) :ymphoplasmacytic lymphoma / immunocytoma d) Mantle cell lymphoma
e) Follicular lymphoma
f) Extranodal marginal zone B-cell lymphoma of MALT type g) Nodal marginal zone B-cell lymphoma (+/- monocytoid B-cells) h) Splenic marginal zone lymphoma (+/- villous lymphocytes) i) Hairy cell leukemia
j) Plasmacytoma/plasma cell myeloma k) Diffuse large B-cell lymphoma
l) Burkitt's lymphoma
T-cell and putative NK-cell
I. Precursor T-cell neoplasm: precursor T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL, LBL)
II. Peripheral T-cell and NK-cell neoplasms
a) T-cell chronic lymphocytic leukemia/prolymphocytic leukemia b) T-cell granular lymphocytic leukemia
c) Mycosis fungoides/Sezary's syndrome
d) Peripheral T-cell lymphoma, not otherwise characterized e) Hepatosplenic gamma/delta T-cell lymphoma
f) Subcutaneous panniculitis-like T-cell lymphoma g) Angioimmunoblastic T-cell lymphoma
h) Extranodal T-/NK-cell lymphoma, nasal type i) Enteropathy-type intestinal T-cell lymphoma j) Adult T-cell lymphoma/leukemia (HTLV 1+)
k) Anaplastic large cell lymphoma, primary systemic type l) Anaplastic large cell lymphoma, primary cutaneous type m) Aggressive NK-cell leukemia
Hodgkin's lymphoma (Hodgkin's disease)
I. Nodular lymphocyte-predominant Hodgkin's lymphoma II. Classical Hodgkin's lymphoma
a) Nodular sclerosis Hodgkin's lymphoma
b) Lymphocyte-rich classical Hodgkin's lymphoma c) Mixed cellularity Hodgkin's lymphoma
Appendix 2
ESAP Chemotherapy Regimen
This can be administered both as an inpatient and an out patient.
Etoposide 40 mg / m2 in 500 ml NS iv over 1-3 hours, daily for 4 days
Solumedrol 500 mg dose iv piggyback, daily for 4 days
Cisplatin 25 mg / m2 / day as a continuous infusion over 24 hours / or bolus over 1-3 hours, daily for 4 days
Ara-C 2 Gm / m2 iv infusion over 2-3 hours, following completion of Cisplatin on Day 5
Magnesium sulphate 1 Gm iv piggyback, daily for 4 days
Routine anti emetic prophylaxis
Repeat q 21 - 28 days
IMVP-16 regime
Ifosfamide 1.25 Gm / m2 iv infusion in 1L NS over 3 hours, daily for 4 days
Mesna 400 mg / m2 iv piggyback 1 dose pre Ifosfamide, and 2 doses, 4 and 8 hours after start of ifosfamide infusion, daily for 4 days
Methotrexate 30 mg / m2 iv push Days 1 and 4
Etoposide 100 mg / m2 iv infusion in 500 ml NS over 2 hours, daily for 3 days
DHAP regime
Dexamethasone 40 mg iv over 15 minutes, daily for 4 days
Ara-C 2 Gm / m2 iv infusion over 3 hours q 12 hours two doses on Day 2 (first dose, immediately after completion of Cisplatin)
Appendix 6
BEAM High Dose Chemotherapy Regime
Day -6 BCNU 300 mg / m2 iv piggyback in NS over 2 hours
Days -5, -4, -3, -2 Etoposide 200 mg / m2 iv piggyback in NS over 1-3 hours, daily for 4 days
Day -5, -4, -3, -2 Ara-C 200 mg / m2 iv piggyback in NS over 3 hours q 12 hours, (twice a day), daily for 4 days
Day -1 Melphalan 140 mg / m2 iv in NS over 1 hour 1 L D5W + 50 mmol NaHCO3 + 20 mmol KCl at
200ml per hour starting same time as Melphalan, continued for 12 hours
Day 0 Re infuse PBSC, 24 hours after end of Melphalan administration
CBV High Dose Regime
Days -5, -4, -3, -2 10.00 am Cyclophosphamide 1.5 Gm / m iv over 1 hour
Mesna 500 mg / m iv piggyback pre
Cyclophosphamide + 2 doses q 4 and 8 hours after start of Cyclophosphamide, daily for 4 days
Day -5 11.00 am BCNU (Carmustine) 300 mg / m iv piggyback in NS over 2 hours
Days -5, -4, -3 8.00 am Etoposide 150 mg / in 1L NS iv over 1-2 hours, q 12 hours, daily for 3 days
Appendix 8
Standing Orders for HDC/ PBSCT
1.Low bacterial diet when ANC < 500 (Appendix 11) 2. Vital signs q shift and prn
3. Daily weight
4. Use irradiated blood products only
5. Heparin 5 ml (50 U / ml) flush b.i.d to unused catheter lumens
6. For each lumen if blocked, call IV team to use TPA 1mg/ml to the blocked catheter, dwell it for 1-2 hrs, may repeat x1 as per IV team and hospital current policy
7. Start neutropenic precaution when ANC < 500 8. laboratory work from day 0
8.1 CBCD and Renal profile Q daily 8.2 Hepatic profile, q.o.d
8.3 Every Saturday urine analysis & culture & sensitivity 9. Sodium bicarbonate mouthwash 30 cc swish and spit Q 6 hour 10.If febrile (> 38ºC) but not neutropenic (ANC > 1000)
a) Blood cultures - peripheral and central b) UA, and Urine C & S, if symptomatic c) Throat swab C & S, if symptomatic d) If cough + sputum, C & S
e) Any skin lesions C & S, if symptomatic
f) If diarrhea +, stool C & S, O & P, Fungal culture, and clos. Diff. Toxin g) CXR within 24 hours
h) If fever persists, blood cultures x 1 Q daily (Peripheral and Central Lines) i) Antibiotic levels as required
11. If febrile (> 38ºC) and neutropenic (ANC < 1000) All of number 10
Inform MD
CEFTAZIDIME 2 GM IV after blood cultures and q 8 hours Other antibiotics as per MD
12. Infection prophylaxis (to be started on day -2, high dose chemotherapy / conditioning regimen
Ciprofloxacin 500 mg PO BID Fluconazole 100 mg PO QD
Appendix 9
General Nursing Instructions for HDC / PBSCT
1. Thorough physical assessment per standard each shift. 2. Check laboratory results q daily.
3. Central venous catheter care per policy.
4. Oral care material to be available in patient's bedside. 5. Irradiated blood products only.
6. No food stored in room or brought from outside. 7. No live plants and no live or dried flowers in room.
8. Shower with Hibiscrub, and shampoo q daily (protect iv sites). 9. Peripheral iv sites re sited q 72 hours.
10. Male patients to use only electric shavers. 11. When patient on neutropenic precaution :
Isolation cart outside room.
Replace all iv tubings q 72 hours, and clean pump daily Stethoscope in room, alcohol wipe after each use
Thermometer in room
Scrubbing hands before and after each entry
*Only one sitter can be allowed after prescreening and teaching Housekeeping to clean room first in am
Physiotherapist / Dietitian to be informed Hand washing before entering room each time
Gowns / gloves necessary only if handling patient / secretions Mask only if risk of transmitting infection
Standard universal precautions as per nursing guidelines
* during patient’s social evaluation and subsequent hospital visits, if patient wishes and felt appropriate by the treating team, nurses and the BMTC, a family member can be allowed to stay with the patient during the neutropenic precaution period. This member will be screened ahead of time for this and will be allowed only if felt appropriate by the team and not resulting in patient care compromise. Many young patients and especially young female patients are likely to benefit from this.
Appendix 10
Dental Clearance Guidelines for Progenitor Cell Transplantation
“Routine” Autologous Autologous Allogenic Allogenic
Chemotherapy PBSCT BMT PBSCT BMT
Immunosuppression + / - yes + yes + yes +++ yes +++
Myelosuppression yes/no yes 2 weeks yes 3-6 weeks yes 2 weeks yes 2-4 weeks
(neutropenia)
Isolation Room no yes yesyes yes
Dental Clearance no yes yesyes yes
Amount of none Only acute acute and
Dental Treatment immediate chronic sources of
for Clearance sources of oral infection
oral infection and irritation
Acute Immediate Source Chronic Source
- fistula - Note: for a more complete list of possible
chronic sources of oral infection and/or oral irritation, - root tips; exfoliating teeth please see attachment - “Oral Care Considerations for
Patients Undergoing Bone Marrow Transplantation”; - pulpal and/or periapical involvement Allard, 19 March 1994
- partial impaction - partial impaction
(ex. Third molar) with inflammation (ex. Third molar) without inflammation
- gross caries into or very near pulp - Note: Buccal pit, occlusal and small Class II, III, are not indicated.
- gross calculus, highly inflammed - slight calculus, slight inflammation - fixed orthodontics
- severe periodontitis - moderate periodontitis
severe mobility, severe bone loss, through and through furation,
The very young patient - only a few months old, with no teeth - would benefit from a brief but important visit to dental clinic. Every effort should be made to arrange such an evaluation while the patient is on the ward or in the Oncology Clinic.
These guidelines are for consideration. They are not meant to imply that every patient will always fit perfectly into a particular slot. These guidelines provide a “yardstick”, a measure, that can be used to compare each patient to this overall “standard”. The clinician will then apply his/her own skills to ascertain if the patient has any individual variation from the “standard”.
Appendix 11
Low Bacterial Diet
Food Group Foods Allowed Foods to Avoid
Milk & Milk Products Laban, Labneh, Cottage Cheese, Cheese, Pasteurized Milk
Unpasteurized Milk or Yoghurt
Fruits and Fruit Juices Canned Fruits and Juices, Fruits with skins that can be peeled off
Fresh and Frozen Fruits and Juices, Raisins, Dates, and other Dried Fruits
Vegetable and Vegetable Juices
All Vegetables allowed if well cooked
Raw Vegetables, All Fresh Salads
Potatoes and Substitutes Cooked Potatoes, Rice, Noodles, Spaghetti, French Fries, Potato and Corn Chips
Bread and Cereals All packaged Bread, Arabic Bread, Cold Cereals, Crackers, Rolls
Meat and Meat Substitutes
All well cooked Meat, Fish and Poultry, Pasteurised Cheese, Eggs cooked with shell removed
Non pasteurised Cheese, rare or medium rare Meats
Fats and Oils Margarine, Butter, Cream Cheese, Salad Dressing, Mayonnaise, Oil shortening used in cooking
Desserts Baked Cakes, Cookies, Pudding,
Mahalabiya
Beverages Coffee, Tea, Decaffeinated Coffee,
Arabic Coffee, Carbonated beverages
Miscellaneous Salt, Sugar, Jam, Jellies, Honey, Syrup, Nuts individually packed, Gravy, Cream Sauces
APPENDIX 12
A Predictive Model for Aggressive Non Hodgkin’s Lymphoma
The International Non Hodgkin’s Lymphoma Prognostic Factors Project NEJM 1993;329:987-94
2031 patients 1982 – 1987
Europe and North America Anthracyclin based therapy
International Prognostic Index All patients and Age Adjusted
All patients Relative risk
Age (< 60 vs > 60 1.96
Serum LDH < 1x vs > 1x 1.85
PS 0-1 vs 2-4 1.80
Stage I-II vs III - IV 1.47
Extranodal Invol < 1 vs >1 1.48
Age Adjusted, Patients < 60
Stage I-II vs III - IV 2.17
PS 0-1 vs 2-4 1.95
Serum LDH < 1x vs > 1x 1.81
Outcome according to risk group defined by IPI and Age-Adjusted IPI
Risk group # of risk factors CR % OS% 2 yr OS % 5 yr All patients Low 0 - 1 87 84 73 Low interm. 2 67 66 51 Hihg interm. 3 55 54 43 High 4-5 44 34 26 Age < 60 Low 0 92 90 83 Low interm. 1 78 79 69 Hihg interm. 2 57 59 46 High 3 46 37 32
APPENDIX 13
FOLLOW-UP GUIDELINES FOR PATIENTS UNDERGOING / UNDERGONE HDC/PBSCT
Follow up of patients undergoing HDC / PBSCT and are in CR / Cru after PBSCT This will not be followed if relapse is suspected clinically after PBSCT
All abnormal studies will be repeated till they become normal or till they are no longer required clinically.
Initial w/u on relapse will include rather comprehensive lab work and test as indicated clinically including BM Bx HODGKINS DISEASE Relapse mid of salvage Rx 2 months post BMT/ XRT Every 3 months Every 6 months Every 1 year History / Physical CBCD/LDH X X X X 6 X 6 X 2 -5 CT scan X X X Gallium X X PET (in place of Gallium) X X Bone Scan Only as indicated MRI Only as indicated
NON HODGKIN’S LYMPHOMA Relapse mid of salvage Rx 2 months post BMT/ XRT Every 3 months Every 6 months Every 1 year History / Physical CBCD/LDH X X X X 6 X 6 X 2 -5 CT scan X X X Gallium
PET Only as indicated Bone Scan
Only as indicated MRI
Only as indicated
50%-60% patients are likely to relapse after PBSCT, most of them with in 2 years A symptomatic patient will get proper work up for palliative treatment decision
