As a developing country it was a great challenge to start the stem cell transplantation first ever in Bangladesh emphasizing from the infrastructure development to the direct patient care at the biggest tertiary public Hospital, Dhaka Medical College Hospital (DMCH). Gratwohl et al conducted a global assessment of hematopoietic stem cell transplants and found that HSCT utilization rates were highly associated with countries with higher gross national income per capita, governmental health care expenditures, and human development index.⁵ With the continuous support of Government of Bangladesh it is now possible to run one of the most expensive and standard treatment in HSCT centre of DMCH with relatively low cost (around $7000-$10,000 ) comparing with the cost of that in developed countries and this is a great opportunity for the poor patients of haematological malignancy in the country.

Introduction of novel agents for multiple myeloma has led to the question of role of front line ASCT as a treatment of the disease. Considering the literature search during 1990s, before the era of novel agents, the several randomized trials have been found investigated the role of conventional chemotherapy versus high dose therapy (HDT) followed by ASCT in younger patients of MM and all of these data,the overall response rate was in favor of ASCT. Most of the trials showed significant benefit in favor of HDT followed by ASCT in terms of higher CR rate and higher rate of EFS. In the French IFM 90 trial autologous BMT versus conventional chemo the result showed higher CR rate (22% Vs 5%), better 5 year EFS (28% Vs 10%) and greater OS (52% Vs 12%).⁶ As a result the front line ASCT became the standard of treatment for young eligible MM patients since then.

In the last decade, introduction of novel agents thalidomide, lenalidomide and bortezomib have markedly improved the CR rate (VGRP 70 % in bortezomib containing regimen Vs 15 % in VAD) both before and after relapse MM without significant toxicities. It was stated that three drugs regimen incorporating bortezomib and dexamethasone with a third one with immune modulatory (Immid) is better than two drugs in MM although superiority of which three drugs combination is yet to be published (eg. RVD [lenalidomide, bortezomib and dexamethasone] and VCD [bortezomib, cyclophosphamide and, dexamethasone] both are of similar efficacy and potency).^7-9

Cavo et al investigated in younger newly diagnosed MM patients to evaluate the efficacy of VTD (bortezomib, thalidomide, dexamethasone) Vs TD (thalidomide & dexamethasone) and the result showed clear benefit of VTD over TD in terms of better CR (38% Vs 23%), VGPR (79% Vs 58%) and PFS favors the VTD arm.¹⁰

In this centre majority (7 out of 11) of the myeloma patients were transplanted after first relapse or subsequent relapse, only 4 patients underwent upfront ASCT at 1^st CR. It is to be mentioned that the median age of MM patients in Bangladesh is earlier than in western countriesand here it was also observed average age of myeloma patients is 49.54 years in this study.² Thusthe ASCT can play an important mode of approach for majority of MM patients considering longer survival and better quality of life. Most of the relapsed/newly diagnosed patients were initially treated with thalidomide + dexamethasone or VAD (vincristine, adriamycin, dexamthasone) chemotherapy, although these protocols are not widely used in recent years due to availability of novel agents. All of them were in VGPR after reinduction with bortezomib containing three drug regimen, either VCD, VTD or RVD. All the myeloma patients were high risk in terms of International Staging System (ISS) prognostic index, but cytogenetic profile was not of high risk panel. As the sample size was too small it could not be concluded the co-relation of cytogenetics with ISS risk staging.

All the MM patients were collected the stem cells using cyclophosphamide and GCSF as soon as they were in at least VGPR.MM patients were conditioned with high dose Inj melphalan 200 mg/m² and observed morbidity was less and the 100 days mortality was nil. Three patients of MM died beyond 400 days on average who had developed significant respiratory tract infection in addition to disease relapse around one year posttransplant period. It is also to be mentioned that relapse after autologous stem cell transplant can be managed with newer novel agents eg carfilzomib, pomalidomide, daratumumab etc., but due to unavailability and high expense of these medicine our patients could not be treated with those agents.

High dose chemotherapy followed by ASCT is the standard of care in chemo sensitive relapse or refractory lymphoma.¹¹ In this new centre, it was treated 18 relapsed /refractory Lymphoma (NHL= 12, HD= 6) patients with BEAM conditioning followed by ASCT. Many relapsed/refractory lymphoma in the country are lately addressed to Hematologist and they are sometimes over treated with several agents that might have impact on chemo resistance. This factis reflected in lower number of transplanted patients at our centre. Patient’s chemo sensitivity was assessed after salvage chemotherapy (RICE, RDHAP, ICE or GND) that were being selected according to disease. Stem cell mobilization was preceded by inj GCSF following 2^nd or 3^rd salvage chemo protocol.^11,12

The average CD34+ cell count collected for all 32 patients was 4.39 x10⁶/kg (range 1.9-14 x10⁶/kg) with mean viability rate of 96%. Engraftment, as defined by sustainedneutrophil count ≥ 0.5 x10⁹/L and unsupported platelet count ≥20 x10⁹/L occurred in all patients (range day 9-16). 

Every patients at the centre gets ice chips during intravenous high dose Melphalan aiming to reduce the oral and upper GIT mucositis. The patients rarely had severe grade III-IV mucositis in the centre. We experience a little more CV line related blood stream infection in the neutropenic period but that did not hamper the engraftment as evidenced the average neutrophil engraftment was on Day +10 and platelet engraftment was on D+11. Eightout of 32 (25%) patients had positive blood CS for Pseudomonas (4), S. Epidermidis (2), Acenatobacter (1) and MRSA (1). Although CMV haemorrhagic cystitis is very rare in Autologous SCT, it was experienced one CMV haemorrhagic cystitis with CMV viremia in one patient who was treated with Inj Gancyclovir and was recovered well. Only one patient need ICU with ventilator support for severe pneumonia and she developed posterior reversible encephalopathy syndrome (PRES) and was managed successfully. Other expected toxicities nausea, emesis, loose stool, transient electrolyte imbalance were within tolerable limit among the patients and were managed accordingly.

Three relapsed AML (Acute Myeloid Leukaemia) was consolidated with standard dose busulfan-cyclophosphamide followed by ASCT as they had no matched donor and there is no scope of haploidentical transplant in Bangladesh. Till now two of them are in good remission status with very good quality of life.

On an average one unit RCC and 1 unit apheretic platelet were needed during the post transplant cytopenicperiod for all patients.  All blood products were being irradiated and leucodepleted. All patients were given Inj GCSF routinely from D+3 until engraftment.

ASCT could significantly improve the overall survival and quality of life in MM and definitely a curative treatment for relapsed or refractory lymphoma. This small experience in the journey of transplant was relatively safe and without any transplant related mortality in first 100 post transplant days. Total 35 patients (five transplants were done after January 2018) have been transplanted with their autologous stem cells in this centre so far. The dedicated team work had enabled us to run the successful transplant program in government sector at DMCH. But the challenges are sustainable financial source and government support and development of human resource as a continuous process. As a new centrethe vision is to launch Allogeneic transplant very soon for aplastic anaemia, thalassemia and haematological malignancies and to establish this as a Centre of Excellence in near future.